Serious Reportable Events

APPENDIX TWELVE. LIST OF SERIOUS REPORTABLE EVENTS IN HEALTH CARE... 

Source Serious Reportable Events in Healthcare A Consensus Report. National Quality Forum, Washington D.C. This list is dynamic and will be updated see www.qualityforum.com. 

The nurse encourages the parents or guardians to report any adverse reactions or serious adverse events occurring after administration of a vaccine It may be necessary to report the event to VAERS. 

Report SERIOUS adverse events. An event is serious when the patient outcome is ... 

If your report Involves a serious adverse event With a device and It occurred in a facility outside a doctor s office, that facility may be legally required to report to FDA and/or the manufacturer. Please notify the person in that facility who would handle such reporting. 

The USP Practitioners Reporting Network is a partner in mf.dWatcm, the FDA s medical products reporting program. As a partner, USP PRN contributes to the FDA s efforts to protect the public health by helping to identify serious adverse events for the agency. This means that your reported information is shared with the FDA on a daily basis, or immediately if necessary. 

Refer lo the Reportable Events Table (RET) for events mandeted for reporting by law. Reporting for other serious events foil to be related but noton the RET is encouraged. 

Notification by originating investigator to sponsor of serious adverse events and related reports... 

Just as there is an adverse event form, there is usually a serious adverse event (SAE) form. Note here that serious as defined by the FDA is different from severe on the adverse event form. A patient can have a severe headache that may not be considered serious. The ICH guideline (also in ICH E3) entitled Clinical Safety Data Management Definitions and Standards for Expedited Reporting defines serious adverse events as follows ... 

Usually a separate CRF is used to capture serious adverse events, as those must be reported to the FDA within 24 hours. That often means that the serious adverse events CRF data and the regular trial CRF adverse events are collected in different data tables, if not entirely different software systems. Pharmaceutical companies often want to reconcile the two databases to ensure that all serious adverse events appear in the regular-trial CRF adverse events database and that any event in the serious adverse events database is flagged properly as serious in the regular CRF adverse events database. 

A large open-label flexible dose study (Sanchez-Lacay etal, 2001) utilizing nefa-zodone in the treatment of major depression in a predominantly monolingual, Hispanic Caribbean population (Dominican Republic, Puerto Rico, and Cuba) revealed similar response rates and an endpoint mean dosage when compared to previous nefazodone trials with non-Hispanic patients. No serious adverse events were reported, but 42% of the subjects did not complete the study for various reasons including side effects, family, or work responsibilities. 

Herbal, natural, and food-supplement products are often used to promote weight loss (Table 59-3). The FDA does not strictly regulate these products, so the ingredients may be inactive and present in variable concentrations. After more than 800 reports of serious adverse events (e.g., seizures, stroke, and death) were attributed to ephedrine alkaloids, the FDA decided to exclude them from dietary supplements. 

The spontaneous report event is categorized as serious or nonserious, expected or unexpected ... 

A periodic report contains certain information, such as the event terms submitted during the period, the dates that events of the period were submitted, an event term count by body system, and labeling changes made due to the period s adverse experiences. In addition to (and prior to) being incorporated into a periodic report, 15-day reports are submitted within 15 calendar days of the date the applicant received the data. All 15-day reports contain serious, unexpected events. Non-15-day reports are submitted periodically in FDA periodic reports. 

An Investigator, not an employee of the Sponsor, is appointed to be responsible for the conduct of a trial. An appropriate quality system is followed and deviations from trial protocols are reported. Serious adverse events have to be reported to regulatory authorities within a specified time. 

Are there clear instructions for reporting of adverse events and serious adverse events (SAEs) There should be full instructions for the reporting of SAEs (including addresses and fax numbers), with time limits. It should be clear that these rules also apply to SAEs that occur in subjects who have finished the study. All SAEs that come to the knowledge of the trialist should be reported unless the protocol provides guidance or time limit when the authors can justify that the occurrence of the SAE could not be related to the treatment received in the clinical trial. In a blinded study, there should be clear instructions on when and by whom the code for a particular study subject should be unblinded in an emergency. 

All serious adverse events, deviations from the protocol, extensions of study period or increase in patient numbers should be reported to the head of the institute by the investigator. 

The investigator shall report all serious adverse events immediately to the sponsor except for those that the protocol or investigator s brochure identifies as not requiring immediate reporting. The immediate report shall be followed by detailed, written reports. The immediate and follow-up reports shall identify subjects by unique code numbers assigned to the latter. 

The most frequently reported serious adverse events reported with cancer chemotherapy patients included death, fever, pneumonia, dehydration, vomiting, and dyspnea. The most commonly reported adverse events were fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea. The most frequently reported reasons for discontinuation of darbepoetin alfa were progressive disease, death, discontinuation of the chemotherapy, asthenia, dyspnea, pneumonia, Gl hemorrhage, thrombotic events, rash, dehydration. 

CYP3A4 inhibitors (eg, macrolide antibiotics, protease inhibitors) There have been rare reports of serious adverse events in connection with the coadministration. Fibrotic complications There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine. Risk of myocardial Ischemia and/or Ml and other adverse cardiac events Do not use dihydroergotamine in patients with documented ischemic or vasospastic coronary artery disease. 

Serious hematological events Two confirmed cases of aplastic anemia and 1 confirmed case of agranulocytosis were reported in the first 11 years of marketing in Japan. 

Aerosol - Several serious adverse events occurred in severely ill infants with life-threatening underlying diseases, many of whom required assisted ventilation. Additional reports of worsening of respiratory status, bronchospasm, pulmonary edema, hypoventilation, cyanosis, dyspnea, bacterial pneumonia, pneumothorax, apnea, atelectasis, and ventilator dependence have occurred. Sudden deterioration of respiratory function has been associated with initiation of aerosolized ribavirin use in infants. If ribavirin aerosol treatment produces sudden deterioration of respiratory function, stop treatment and reinstitute only with extreme caution, continuous monitoring, and consideration of coadministration of bronchodilators. 

Underlying respiratory disease Zanamivir has not been shown to be effective and may carry risk in patients with severe or decompensated COPD or asthma, and serious adverse events have been reported in such patients. Therefore, zanamivir is not generally recommended for treatment of patients with underlying airways disease such as asthma or COPD. 

The safety of G-CSF stimulation in patients with CAD has been questioned in two recent studies. Hill et al. [138] report the results of administration of 10 mcg/kg/day of G-CSF for 5 days in patients with chronic CAD n = 16). There was no clinical benefit as assessed by exercise stress testing and dobuta-mine cardiac MRI. Additionally two patients in the G-CSF group developed serious adverse events related to the therapy (one non-ST elevation MI one MI causing death). Zbinden et al. [139] also tested the efficacy of the same G-CSF dose in patients with chronic CAD ( = 7). The invasive endpoint collateral flow index was significantly better in the G-CSF treated patients when compared to the placebo group. However, two patients in the G-CSF treated group developed acute coronary syndrome during treatment. 

There is only one study in (open trial) examining the efficacy of quetiapine in the treatment of EOS (Mc-Conville et ah, 2000). Patientes were treated with 100 or 400 mg/day. Quetiapine was well tolerated and improved both positive and negative symptoms as determined by the BPRS, the CGI Scale, and the Modified SANS. Quetiapine pharmacokinetics were dose proportional in adolescents and resembled those reported in adult patients. The most common side effects in the study were postural tachycardia and insomnia. The EPS occurred and improved during the course of treatment. There were no serious adverse events or clinically important changes in hematology or clinical chemistry. 

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